Farxiga®Xigduo®XR (as a combination product containing Dapagliflozin, Metformin)
AUDIENCE: Pharmacy, Emergency Medicine
ISSUE: An FDA safety review has resulted in adding warnings to the labels of a specific class of type 2 diabetes medicines called sodium-glucose cotransporter-2 (SGLT2) inhibitors about the risks of too much acid in the blood and of serious urinary tract infections. Both conditions can result in hospitalization.
FDA issued a Drug Safety Communication in May 2015 warning about the risk of ketoacidosis with SGLT2 inhibitors and alerting that the Agency would continue to evaluate this safety issue. A review of the FDA Adverse Event Reporting System (FAERS) database from March 2013 to May 2015 identified 73 cases of ketoacidosis in patients with type 1 or type 2 diabetes treated with SGLT2 inhibitors. Symptoms of ketoacidosis include nausea, vomiting, abdominal pain, tiredness, and trouble breathing.
FDA also identified 19 cases of life-threatening blood infections (urosepsis) and kidney infections (pyelonephritis) that started as urinary tract infections with the SGLT2 inhibitors reported to FAERS from March 2013 through October 2014. All 19 patients were hospitalized, and a few required admission to an intensive care unit or dialysis in order to treat kidney failure.
As a result, FDA added new Warnings and Precautions to the labels of all SGLT2 inhibitors to describe these two safety issues, and to provide prescribing and monitoring recommendations. FDA is also requiring manufacturers of SGLT2 inhibitors to conduct a required postmarketing study. This required enhanced pharmacovigilance study requests that manufacturers perform analyses of spontaneous postmarketing reports of ketoacidosis in patients treated with SGLT2 inhibitors, including specialized follow-up to collect additional information, for a period of 5 years.
BACKGROUND: SGLT2 inhibitors are a class of prescription medicines that are FDA-approved for use with diet and exercise to lower blood sugar in adults with type 2 diabetes. Medicines in the SGLT2 inhibitor class include canagliflozin, dapagliflozin, and empagliflozin.
RECOMMENDATION: Patients should stop taking their SGLT2 inhibitor and seek medical attention immediately if they have any symptoms of ketoacidosis.
Health care professionals should assess for ketoacidosis and urinary tract infections in patients taking SGLT2 inhibitors who present with suggestive symptoms. Ketoacidosis associated with the use of SGLT2 inhibitors can occur even if the blood sugar level is not very high. If ketoacidosis is suspected, the SGLT2 inhibitor should be discontinued and treatment instituted promptly.
For more information visit the FDA website at: Web Siteand Web Site.
Dapagliflozin is used along with diet and exercise, and sometimes with other medications, to lower blood sugar levels in patients with type 2 diabetes (condition in which blood sugar is too high because the body does not produce or use insulin normally). Dapagliflozin is in a class of medications called sodium-glucose co-transporter 2 (SGLT2) inhibitors. It lowers blood sugar by causing the kidneys to get rid of more glucose in the urine. Dapagliflozin is not used to treat type 1 diabetes (condition in which the body does not produce insulin and, therefore, cannot control the amount of sugar in the blood) or diabetic ketoacidosis (a serious condition that may develop if high blood sugar is not treated).
Over time, people who have diabetes and high blood sugar can develop serious or life-threatening complications, including heart disease, stroke, kidney problems, nerve damage, and eye problems. Taking dapagliflozin, making lifestyle changes (e.g., diet, exercise, quitting smoking), and regularly checking your blood sugar may help to manage your diabetes and improve your health. This therapy may also decrease your chances of having a heart attack, stroke, or other diabetes-related complications such as kidney failure, nerve damage (numb, cold legs or feet; decreased sexual ability in men and women), eye problems, including changes or loss of vision, or gum disease. Your doctor and other healthcare providers will talk to you about the best way to manage your diabetes.
Dapagliflozin comes as a tablet to take by mouth. It is usually taken with or without food once a day in the morning. Take dapagliflozin at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take dapagliflozin exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Your doctor may start you on a low dose of dapagliflozin and increase your dose if needed.
Dapagliflozin controls type 2 diabetes but does not cure it. Continue to take dapagliflozin even if you feel well. Do not stop taking dapagliflozin without talking to your doctor.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with dapagliflozin and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website ( Web Site) to obtain the Medication Guide.
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
Before taking dapagliflozin, tell your doctor and pharmacist if you are allergic to dapagliflozin, any other medications, or any of the ingredients in dapagliflozin tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention diuretics ('water pills') and any medications for high blood pressure.tell your doctor if you are on dialysis and if you have or have ever had kidney disease. Your doctor may tell you not to take dapagliflozin.tell your doctor if you are on a low sodium diet or have or have ever had low blood pressure, bladder cancer, or yeast infections in the genital area. If you are male, tell your doctor if you have never been circumcised.tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking dapagliflozin, call your doctor.if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking dapagliflozin.alcohol may cause a change in blood sugar. Ask your doctor about the safe use of alcoholic beverages while you are taking dapagliflozin.you should know that dapagliflozin may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. If you have this problem, call your doctor. This problem is more common when you first start taking dapagliflozin. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.ask your doctor what to do if you get sick, develop an infection or fever, experience unusual stress, or are injured. These conditions can affect your blood sugar and the amount of dapagliflozin you may need.
Be sure to follow all exercise and dietary recommendations made by your doctor or dietitian. It is important to eat a healthful diet and exercise regularly.
Follow your doctor's instructions about drinking enough fluids throughout the day while you are on this medication.
Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
This medication may cause changes in your blood sugar. You should know the symptoms of low and high blood sugar and what to do if you have these symptoms.
Dapagliflozin may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
urinating a lot, including at nightincreased thirst
Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately: frequent, urgent, burning, or painful urinationurine that is cloudy, red, pink, or brownstrong smelling urinepelvic or rectal pain(in women) vaginal odor, white or yellowish vaginal discharge (may be lumpy or look like cottage cheese), or vaginal itching(in men) redness, itching, or swelling of the penis; rash on the penis; foul smelling discharge from the penis; or pain in the skin around the penisweaknessdry mouth, nausea, vomiting, stomach pain, unusual fatigue or tiredness, breath that smells fruity, decreased consciousness, or confusion
If you experience any of the following symptoms, stop taking dapagliflozin and call your doctor immediately or get emergency medical treatment: rashhivesitchingdifficulty breathing or swallowingswelling of the face, throat, tongue, lips, eyes, hands, or feethoarseness
Dapagliflozin may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online ( Web Site) or by phone (1-800-332-1088).
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).
Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website ( Web Site) for more information if you do not have access to a take-back program.
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
Keep all appointments with your doctor and the laboratory. Your blood sugar levels should be checked regularly to determine your response to dapagliflozin. Your doctor will order other lab tests, including glycosylated hemoglobin (HbA1c), to check your response to dapagliflozin. Your doctor will also tell you how to check your response to this medication by measuring your blood sugar levels at home. Follow these instructions carefully.
Before having any laboratory test, tell your doctor and the laboratory personnel that you are taking dapagliflozin. Because of the way this medication works, your urine may test positive for glucose.
You should always wear a diabetic identification bracelet to be sure you get proper treatment in an emergency.
Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
AHFS® Consumer Medication Information. © Copyright, The American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland. All Rights Reserved. Duplication for commercial use must be authorized by ASHP.
Selected Revisions: December 15, 2015.